Associations were found between disease severity or transepidermal water loss and TH2 (IL-33 and IL-4R) and TH17/TH22 (IL-36G and S100As) products in lesional and nonlesional AD skin (evaluated using the SCORing Atopic Dermatitis, Eczema Area and Severity Index, and Pruritus Atopic Dermatitis Quickscore tools).
The production of pro-allergic cytokines, TSLP and IL-33, as well as the cell populations of their target cells DCs and ILC2s were decreased in AD model, respectively.
From these results, we suggest that IL-33-induced AD-like inflammation is dependent on innate immune responses that are mediated by ILC2s in concert with basophils.
In this review, we focus on the recent advances of the underlying intercellular and intracellular mechanisms by which IL-33 can regulate the allergic inflammation in various allergic diseases including allergic asthma and atopic dermatitis.
IL-33 is a pro-inflammatory cytokine which mediates several immune functions; its involvement in a wide range of diseases, such as atopic dermatitis, asthma, and rheumatoid arthritis, is now emerging.
Application of indomethacin, which blocks prostanoid synthesis, leads to enhanced TSLP and IL-33 production in the skin, increased serum IgE levels, and exacerbation of skin inflammation in this AD model.
The increased expression of PKIα and tight junction (TJ) proteins, with reduced TSLP and IL-33, was also detected in miR-155-5p-blocked mice, in both the initial and elicitation stages of AD.
The emergence of IL-33 as a key molecular player in the development and propagation of widespread inflammatory diseases, including asthma and atopic dermatitis, has established the need for effective IL-33-neutralizing biologics.
These human in vivo findings confirm an IL-33 upstream role in modulating skin inflammatory cascades and define the therapeutic potential for IL-33 inhibition in human diseases, including AD.
Lentivirus-mediated in vitro assays identified that knockdown of SHARPIN can induce elevated expression of IL-33 and its orphan receptor ST2, FLG and STAT3 and NF-κB inactivation in HaCaT keratinocytes, which has been widely evidenced in regulating AD development.
These findings provide evidence that IL-33 induced secretion of IL-31 from LAD2 MC, an action augmented by novel neuroimmune interactions that may help in the development of new treatments of allergic and inflammatory diseases, especially AD and mastocytosis.
Aberrant signaling by IL-33 has been implicated in the pathogenesis of several acute and chronic inflammatory diseases, including asthma, atopic dermatitis, rheumatoid arthritis and ulcerative colitis among others.
Furthermore, we found that eupatilin suppressed the levels of serum immunoglobulin E (IgE), interleukin-4 (IL-4), and AD involved cytokines, such as tumor necrosis factor α (TNFα), interferon-γ (IFN-γ), IL-1β, and thymic stromal lymphopoietin (TSLP), IL-33, IL-25 and increased the levels of filaggrin and loricrin in the oxazolone-induced AD-like mouse model.
In this article, we will focus on the cytokines, interleukin (IL)-17, IL-19, IL-33, and TSLP (thymic stromal lymphopoietin), which play a significant role in AD pathogenesis and may become the targets for future biologic therapies in AD.
Recent insight has identified a number of novel pathways as treatment targets for AD, including the T-helper type 2 cytokines, interleukins (IL) 4, IL-13, IL-33, phosphodiesterase E 4, and Janus kinase signaling.
Emerging data now suggest that epithelial cell-derived cytokines such as thymic stromal lymphopoietin (TSLP), IL-33, and IL-25 may drive the progression from atopic dermatitis to asthma and food allergy.
We also identified upregulated mRNA and protein expression of TLR1, TLR6, IL-25, and IL-33 in human atopic dermatitis skin lesions with high house dust mite sensitization.
Furthermore, skin from ZDHHC13-deficient mice has both elevated levels of IL-33 and type 2 innate lymphoid cells, reinforcing the role of innate immunity in the development of atopic dermatitis.